a. Field of the Invention
This invention relates to pyridylmethyl esters of N-(phenoxyalkanoyl)peptides having valuable pharmaceutical properties, to intermediates for preparing the pyridylmethyl esters, to processes for preparing said esters and intermediates, and to a method for using the pyridylmethyl esters.
B. Prior Art
The association of excessive plasma concentrations of lipoproteins or of plasma lipids with increased risk of heart attack, stroke, and sudden death is well established. Consequently, the consensus of informed opinion is that elevated levels of cholesterol and/or triglycerides should be reduced by appropriate longterm therapy.
The generally accepted Frederickson-Levy-Lees classification of lipid disorders based on lipoprotein disturbances lists five categories, Types I to V, of hyperlipoproteinemia. This classification allows a more rational choice of therapeutic programs for the treatment of hyperlipoproteinemia, see R. I. Levy, Fed. Proc. 30, 829 (1971). Although a variety of drugs are available for the treatment of hyperlipoproteinemia, none of them are suitable for the general treatment of the disease. Thus, at the present time, the preferred drugs for treating the disease are dependent on the classification of the lipid disorder and are different for each class; for example, see R. S. Lees and D. E. Wilson, New. Engl. J. Med., 284, 186 (1971).
The pyridylmethyl esters of this invention have been found now to be effective for reducing levels of cholesterol and triglycerides in the blood of warm blooded animals suffering from hyperlipoproteinemia and associated conditions. The pyridylmethyl esters are effective at dosages which do not elicit undesirable side effects. Furthermore, the esters are effective for treating a broad sector of the population suffering from the disease and find use for the treatment of Types II, III, IV and V hyperlipoproteinemia in general.
The pyridylmethyl esters of this invention are prepared by a convenient process from readily available starting materials. Consequently, the esters are inexpensive and readily available.
The pyridylmethyl esters of this invention feature a new combination of three chemical subunits; namely, a phenoxyalkanoyl group and a pyridylmethyloxy group joined together by a peptide group. Related prior art compounds include 3-pyridylmethyl esters of phenoxyalkanoic acid, U.S. Pat. No. 3,369,025, issued Feb. 13, 1968 and N-(carboxyalkyl)-phenoxyalkanoic acid amides, U.S. Pat. No. 3,364,249, issued Jan. 16, 1968. The prior art compounds are distinguished from the compound of the present invention in that they contain only two of the aforementioned subunits.